rs959181

Positions:

• chr15-84826346-A-G
• chr15-84826346-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020778.5(ALPK3):​c.183-1138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,170 control chromosomes in the GnomAD database, including 54,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54675 hom., cov: 31)
• Consequence: ALPK3 NM_020778.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

Genes affected

ALPK3 (HGNC:17574): (alpha kinase 3) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in cardiac muscle cell development. Predicted to be active in nucleus. Implicated in hypertrophic cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK3	NM_020778.5	c.183-1138A>G		intron_variant		ENST00000258888.6	NP_065829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6	c.183-1138A>G		intron_variant		1	NM_020778.5	ENSP00000258888.6

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128399 AN: 152050 Hom.: 54624 Cov.: 31

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.817

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.830

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.844 AC: 128504 AN: 152170 Hom.: 54675 Cov.: 31 AF XY: 0.840 AC XY: 62500 AN XY: 74378

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.826

Alfa AF: 0.830 Hom.: 6132

Bravo AF: 0.850

Asia WGS AF: 0.867 AC: 3016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs959181; hg19: chr15-85369577;